title: Effect of increasing glutathione with cysteine and glycine supplementation on mitochondrial fuel oxidation, insulin sensitivity, and body composition in older HIV-infected patients.
abstract: BACKGROUND
  HIV-infected patients are reported to have impaired oxidation of fatty acids despite increased availability, suggesting a mitochondrial defect. We investigated whether diminished levels of a key mitochondrial antioxidant, glutathione (GSH), was contributing to defective fatty acid oxidation in older HIV-infected patients, and if so, the metabolic mechanisms contributing to GSH deficiency in these patients.
  
  
  METHODS
  In an open-label design, 8 older GSH-deficient HIV-infected males were studied before and after 14 days of oral supplementation with the GSH precursors cysteine and glycine. A combination of stable-isotope tracers, calorimetry, hyperinsulinemic-euglycemic clamp, and dynamometry were used to measure GSH synthesis, fasted and insulin-stimulated (fed) mitochondrial fuel oxidation, insulin sensitivity, body composition, anthropometry, forearm-muscle strength, and lipid profiles.
  
  
  RESULTS
  Impaired synthesis contributed to GSH deficiency in the patients and was restored with cysteine plus glycine supplementation. GSH improvement was accompanied by marked improvements in fasted and fed mitochondrial fuel oxidation. Associated benefits included improvements in insulin sensitivity, body composition, anthropometry, muscle strength, and dyslipidemia.
  
  
  CONCLUSIONS
  This work identifies 2 novel findings in older HIV-infected patients: 1) diminished synthesis due to decreased availability of cysteine and glycine contributes to GSH deficiency and can be rapidly corrected by dietary supplementation of these precursors and 2) correction of GSH deficiency is associated with improvement of mitochondrial fat and carbohydrate oxidation in both fasted and fed states and with improvements in insulin sensitivity, body composition, and muscle strength. The role of GSH on ameliorating metabolic complications in older HIV-infected patients warrants further investigation.
authors.affiliation: Translational Metabolism Unit (D.N., R.V.S.), Division of Diabetes, Endocrinology, and Metabolism; Diabetes and Endocrinology Research Center (D.N., R.V.S.); and Department of Medicine (J.W.H., F.J.), U.S. Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Dan
authors.initials: D
authors.lastname: Nguyen
authors.forename: Jean W
authors.initials: JW
authors.lastname: Hsu
authors.forename: Farook
authors.initials: F
authors.lastname: Jahoor
authors.forename: Rajagopal V
authors.initials: RV
authors.lastname: Sekhar
mesh_terms: D000367:Age Factors; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001823:Body Composition / Q000187:drug effects*; D003545:Cysteine / Q000008:administration & dosage*; D019587:Dietary Supplements; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism*; D005998:Glycine / Q000008:administration & dosage*; D015658:HIV Infections / Q000178:diet therapy / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D005978:Glutathione; D003545:Cysteine; D005998:Glycine